Method and apparatus for cascade impactor testing of inhalable drug therapies recovery for chemical analysis

ABSTRACT

A compact cascade impactor is formed to classify particles carried in a flow through the impactor. The impactor has collection chambers that are arranged to conserve space and yet provide a large flow passageway. The collection chamber may be tear drop shaped and being nested together. The impactor includes nozzles that are used across a desired range without.

CROSS REFERENCE TO RELATED APPLICATION

[0001] This application is a continuation-in-part of U.S. patentapplication Ser. No. 09/567,552 filed May 5, 2000 for Efficient HighProductivity Cascade Impactors which claims priority on provisionalapplication Ser. No. 60/138,742, filed Jun. 11, 1999, for COMPACT,HIGH-PRODUCTIVITY CASCADE IMPACTORS.

BACKGROUND OF THE INVENTION

[0002] The present invention relates to recovering and handling foranalysis samples comprising a particle impactor. Cascade impactors arewidely used for size distribution measurement of aerosols. For purposeof this invention, particles suspended in a gas are referred to as anaerosol. The gas borne particles can be a solid, a liquid, or a mixtureof both. The particle size is usually between 0.002 um and 100 um.

[0003] Impactor is an aerosol-sampling device for collecting aerosolparticles onto a substrate by the inertial effect of the particles. Onestage of the device usually consists of a nozzle plate in closeproximity to a collection plate. The nozzles in each plate which are ofsubstantially the same size, accelerate the gas to a high velocity. Thegas jets then impinge on the collection plate to cause particlecollection by inertia. The particle size at which 50% of the particlesare collected is known as the impactor cut-point. A cascade impactor isthen several impactor stages in series, arranged so that the largerparticles with large nozzle openings are collected first, followed bysmaller and smaller particles.

[0004] Cascade impactors are widely used for size distribution analysisof aerosol particles. Particulate air pollutants, aerosols in the workplace environment, as well as other aerosols of practical interest areusually polydiverse, with particle sizes spread over a wide range ofvalues. Cascade impactors can be used to separate particles by size intonarrower size intervals. The collected particles can then be analyzed todetermine their mass size distribution or their chemical composition asa function of particle size.

[0005] An important application of the cascade impactor is thedetermination of size distribution of therapeutic aerosols produced byaerosol drug delivery devices such as the metered dose inhaler (MDI) andthe dry-powder inhaler (DPI). Traditionally, drugs delivered in aerosolform have been used to treat asthma and other respiratory diseases.Recently, insulin delivered in aerosol form has also been foundeffective for the treatment of diabetes. Aerosol drug delivery isbecoming increasingly important and the use of cascade impactor fortesting aerosol drug delivery devices is also becoming more wide spread.For such applications, large numbers of impactor samples must beanalyzed for their medicinal content. The accuracy and the efficiencywith which the cascade impactor samples can be recovered and analyzedare becoming increasingly important.

[0006] Because impactor testing of drug delivery devices is very laborintensive, attempts have been made to improve the impactor design tomake the process more efficient. The parent application identified aboveand included as part of this disclosure describes several approaches toimproving the productivity of impactors. Methods to monitor theperformance of the impactor are described in U.S. patent applicationSer. No. 09/360,466 filed Jul. 23, 1999 to ensure consistency ofoperation. Productivity is limited by present particle recoverytechniques.

FOR RECOVERY OF PARTICLES

[0007] The common practice now routinely used in the laboratories torecover samples from impactors for chemical analysis is to manuallyplace the impactor plate or cup (called substrates) on which theparticles are collected in a beaker or in a funnel attached to avolumetric flask and to add solvent to dissolve the chemical compound ofinterest. The solution is then transferred to a sample vial by a syringeor pipette for chemical analysis by the High Performance LiquidChromatograph (HPLC) or ultraviolet spectroscopy. The usual samplerecovery process involves the following steps:

[0008] 1. Disassemble the impactor and remove the sample substrates

[0009] 2. Place the substrates into separate containers, such as beakersor petri dishes. For cascade impactors, as shown herein, separatecontainers are needed, one for each substrate.

[0010] 3. A measured amount of solvent, such as methanol, is added to asubstrate container. This would involve the separate steps of using apipette to draw the required volume of the solvent, for instance, 25 ml,from the solvent reservoir, and releasing the solvent into the substratecontainer.

[0011] 4. The substrate is allowed to remain in the container until thecollected sample is dissolved into the solvent.

[0012] 5. A syringe is used to withdraw the required volume of sample,for example, 1 ml, from the substrate container, and inject into asample vial.

[0013] Steps 3, 4 and 5 usually must be repeated a total of eight to tentimes, one for each of the sample substrate following sample transfer toa vial, the unused solution in the container is discarded, and thecontainer and the impaction plate or substrate must then be cleaned forreuse.

[0014] Because of the many manual steps involved in sample recovery andimpactor cleaning, a laboratory technician may take ½ to one hour torecover the samples from one impactor test run and to prepare theimpactor for re-use. Because of the tedious and repetitive nature ofthese and related tasks, robotic impactor testing systems have beendeveloped, for example, Novi Systems has developed a robotic system thatmimics the human steps involved in sample recovery. The efficiency andspeed equals the human operator, but run around the clock and aresubstantially error free. Robotic systems are expensive and canmalfunction which shuts down the entire system.

SUMMARY OF THE INVENTION

[0015] The present invention provides for appliances to facilitate theuse of cascade impactors for metered-dose and dry-powder inhaler testingincluding the various steps of substrate coating, particle dissolution,sample acquisition, waste solvent disposal, and washing and rinsing thesubstrates. It includes apparatus and procedure to make sample recoveryto be more efficient, more repeatable, and with consistency.

[0016] The present invention uses individual appliances or stations forcarrying out the required steps with various levels of mechanization,including manually operated, computer driven, semi-automatic and roboticappliances. The individual substrates as shown, a cup tray for examplethat has sample cups in it with the classified particles carried in thecup and classified according to the structure and description shown inthis application. The tray is placed into a support, in the dissolutionstation and solvent that will dissolve the chemical or component ofinterest is dispensed by an automatic solvent dispenser in each cup. Aswill be shown this can be done either manually, semi-automatically, orutilizing a grid type syringe carrier, fully automatically. Computercontrols are used for most of these steps and can be programmed to drivea syringe carrier in two mutually perpendicular directions to registerthe carrier with any of the cups desired according to the input program.The solvent dispenser is controlled automatically as well, to dispensethe required solvent in, and if the particles are collected onsubstrates that are removable as small plates from the impactor, thesesubstrates will be place into a separate cup tray so that solvent can beadded to extract the sample.

[0017] Agitation can be provided by fluid motion, that is drawing in aportion of the liquid sample and expelling it back into the cup holdingit, or by ultrasonic vibration, stirring, or similar agitationtechniques.

[0018] Then, a syringe can be moved into a required position for sampletransfer, by drawing a portion of the sample into the syringe and movingit then to a place where it would be dispensed into a vial through aseal septum. Again, the movement of a syringe used to withdraw samplescan be done on a computer controlled three axis handler.

[0019] To accurately measure the amount of solvent dispensed, acalibration cell is used for weighing by electronic balance after theparticles of interest have been dissolved.

[0020] The apparatus shown can also be used for manual manipulation,rocking, decanting and the like. Different types of supports, cups andother apparatus can also be used.

[0021] In the process, the cups or the substrates for collectingparticles can be treated with a coating that is “anti-bounce” coating asan optional step. Further the particular types of washing stations andholders can be varied as desired.

[0022] The present invention thus discloses methods and apparatuses forworking with cascade impactors as they are used for testing metered-doseand dry-powder inhalers for recovering samples that are provided fromexisting cascade impactors, in an efficient and low cost manner.

[0023] BRIEF DESCRIPTION OF THE DRAWINGS

[0024]FIG. 1 is a side view of an impactor made according to the presentinvention;

[0025]FIG. 2 is a top plan view thereof with parts broken away;

[0026]FIG. 3 is a top plan view thereof with the top cover removed;

[0027]FIG. 4 is a sectional view taken as on line 4-4 in FIGS. 2 and 3;

[0028]FIG. 5 is a sectional view taken as on line 5-5 in FIGS. 2 and 3;

[0029]FIG. 6 is a sectional view taken as on line 6-6 in FIG. 2;

[0030]FIG. 7 is a perspective sectional view of a modified form of theinvention;

[0031]FIG. 8 is a vertical sectional view of a further modified form ofthe present invention;

[0032]FIG. 9 is a schematic side sectional view of a typical cascadeimpactor with three impactor stages showing removable impaction plates,that can be slid in and out of the impactor;

[0033]FIG. 10 is a block diagram of the analysis method of the presentinvention;

[0034]FIG. 11 is a top plan view of a tray holding cups with samples inthem, which is removed from the impactor in the first form of theinvention shown in FIGS. 1 through 7;

[0035]FIG. 12 is a sectional view of a typical sample recovery stationmade according to the present invention showing a syringe that is usedfor injecting a solvent into each of the cups, and providing formounting all of the cups from a single sample run of the impactor ofFIG. 1 in a unitary assembly;

[0036]FIG. 13 is an end view schematically shown of the device of FIG.12;

[0037]FIG. 14 is a schematic cross sectional view of a typical solventholding tray in which separate substrates can be placed, such as thoseshown in the second, third, and fourth forms of the invention, forobtaining the samples in a solvent;

[0038]FIG. 15 is an exploded schematic view of a typical three axisholder for a syringe shown schematically adjacent a cross section of asample recovery tray;

[0039]FIG. 16 is a plan view of the system shown in FIG. 9, illustratedschematically;

[0040]FIG. 17 is a schematic representation of sample extraction with apumping action for stirring the substrate;

[0041]FIG. 18 is a schematic cross sectional view of a calibration cellin which solvent can be placed both before adding to a cup, andafterwards, for calibrating the system;

[0042]FIG. 19 is a schematic representation in cross section of astation in which a sample recovery cup or impactor plate can be coatedwith an anti-bounce material;

[0043]FIG. 20 is a schematic cross sectional view of a dissolution andsample acquisition typical wash station that can be used with thepresent invention, that also can be used as a wash station after thesamples have been recovered; and

[0044]FIG. 21 is a sectional view taken on line 21-21 in FIGS. 20 and22;

[0045]FIG. 22 is a view of a manual station similar to FIG. 20;

[0046]FIG. 23 is a plan view of a manual, wash and dry manifold usedwith a tray full of cups;

[0047]FIG. 24 is an end view of FIG. 23; and

[0048]FIG. 25 is a chart showing various combinations of steps in samplehandling.

DETAILED DESCRIPTION OF THE ILLUSTRATIVE EMBODIMENTS

[0049] A first form of the invention illustrated in FIGS. 1 through 6comprises an impactor assembly 10, which has a housing assembly 12, withan aerosol inlet 14 of standard size described in USP 24, Section 601.The inlet can be a standard USP type inlet tube. A pre-separator 16 isillustrated on the inlet in FIG. 1, and it is used to separate out largeparticles with a standard type impactor arrangement.

[0050] The aerosol that is passed through the impactor 10 is an aerosolgenerated by a hand-held. inhaler 17 or other device that may be aliquid or dry powder drug inhaler, such as those used to control asthmaand similar problems. The amount of flow from each charge is small, sothe internal volume of the impactor 10 must be kept low. For testing drypowder inhalers, accepted methods call for the total volume of sampledair to be between 2 liters and 4 liters. Therefore, the internal volumeof the impactor must be low to achieve proper particle sizing. Theinternal volume or dead volume is preferably 1 to 2.5 liters. Small deadvolume is important for achieving steady state flow during a typicalbreath volume of 2 to 4 liters. Steady state flow is achieved in about0.2 seconds. The entire test is completed in 2 to 4 seconds. The flowrate through the impactor will be generated in a selected manner, forexample by providing a vacuum pump such as that shown at 20 on anexhaust or flow outlet opening 22 from the impactor housing 12.

[0051] The impactor 10 of the first form of the invention is made to becompact so that it is easily used, portable and does not take up muchspace, and can be operated in a normal manner. The impactor 10 of thefirst form of the invention has a lid or cover 24 that is sufficientlythick to include flow passageways on the underside. The lid or cover 24has the inlet 14 at one end thereof. The lid or cover 24 is hinged alongone edge to a base frame 25 that has a number of egg shaped or tear dropshaped openings that receive and support tear drop shaped impactorparticle collection chambers or cups as will be shown.

[0052] As shown in FIGS. 3, 4, 5 and 6 a seal plate 30 is positionedjust below the cover or lid 24 and as will be explained, has seals onboth sides to seal passageways on the underside of the cover and, on theopposite or bottom side of the seal plate, to seal around lips of eachof the impaction chambers or cups to define sealed passageways forforming the flow path. The collection chambers or cups will beindividually numbered in this description. The first cup at the inlet isshown at 34, and is larger than the rest. Inlet opening 14 in cover 25opens through an inlet opening 32 that sealingly opens through the sealplate 30 and cover or lid 24 into a chamber or passageway 34A defined bythe first impaction stage cup 34. Cup 34 fits through an opening in acup retainer tray or frame 36. The cup 34 has a peripheral flange 34Bthat rests on the tray or frame 36. The cup also fits in an opening 34Ein the frame 25. The tray or frame 36 is supported on the top of thebase 25.

[0053] The impaction cups are tear drop shaped as shown. The bottom wallat the large end 34E of the first stage cup (and all cups) forms theimpactor surface and underlies the inlet opening 32. The flange 34B ofthe cup 34 is sealed with a seal 34D on the seal plate and extendstransversely of the impactor to a vertical passageway 38 that opensthrough the seal plate 30 to interface or crossover passage 40 formed onthe underside of the cover 24.

[0054]FIG. 3A is a bottom view of the base, with the cups and seal plateremoved, so the interstage passages on the underside of the cover 24 canbe seen. The openings in the cups on the base frame 25 are designatedwith the cup number followed by the letter “E”. The seals on theperipheral flanges of the cups follow the shape of the cup openings inframe 25 shown in FIG. 3A; and as shown in dotted lines in FIG. 3.

[0055] The crossover or interstage passageway 40 leads to a nozzlepassageway or opening in seal plate 30 (FIGS. 3 and 6) having a nozzle44 that has openings 44A of desired size, and desired number. Particleswill discharge into a second stage impactor surface of a cup 46 held inan opening 46E of base 25, under nozzle 44. The tear drop shaped cup 46has a wide end under the nozzle 44 and a narrow opposite end. The cup 46has a flange 46B for support and defines a passageway 46A. The small endof the cup 46 aligns with a passageway or port 50 through the seal plateand opens to a tear drop shaped passageway 54 in the cover 24.

[0056] The large end 54B of passageway 54 overlies an opening in sealplate 30 which holds a nozzle 56 that has openings 56A. Nozzle 56overlies a tear drop shaped cup 58. The openings 56A are smaller andgreater in number than the openings 44A, and the nozzle openingsdecrease in size in the impactor stages to the outlet. The third stageimpactor cup 58 has a flange 58B and forms a passageway 58A (see FIGS.3, 3A and 5) that opens to a vertical passageway 60 in seal plate 30 andto a passageway 62 in the cover 24. That in turn connects to a nozzle 64that discharges into a cup 66.

[0057] A passageway 64A that extends laterally opens through seal plate30 and connects to a tear drop shaped passageway 70 in the cover 24which directs flow through a nozzle 72.

[0058] A cup 74 with a flange 74B provides a fifth stage impactor andunderlies the nozzle 72 and receives particles discharged through thenozzle 72. The cup 74 also forms a passageway 74A leading to an opening76 and to a passageway 78 in the underside of cover 24. Cup 74 fits inopening 74E in the base, shown in FIG. 3A. Cups 66 and 74 are also shownin FIG. 1, where the impactor cover and seal plate are broken away.

[0059] The crossover passageway 78 carries flow to a nozzle 80, withopenings 80A, so flow goes downwardly into an underlying sixth stageimpactor cup 82 supported with a flange 82B. The cup 82 forms animpaction plate and provides a passageway 82A. Passageway 82A leads toan opening 84 and then to a passageway 86 in the underside of cover 24.

[0060] The passageway 86 leads to a nozzle 88 that has openings 88A thatopen to an underlying cup 90 forming a seventh impaction stage. The cup90 is supported on a flange 90B and forms a passageway 90A that leadsthrough an opening 92 to a passageway 94 in the cover 24.

[0061] The passageway 94 opens to a final stage micro orifice filternozzle 96. The micro orifice filter nozzle 96 discharges the flow intoan underlying cup 98 with a support flange 98B that opens to the fluidflow outlet passage 22 from the impactor.

[0062] The seal plate 30, as shown, and as was explained, has “O” ringtype seals for the passageways in the cover and to seal on the impactorcup flanges.

[0063] The passageways in the cover that connect between nozzles are allsealed with tear drop shaped O-ring seals. Passageways 40, 54, 62, 70,78, 86, and 94 are sealed with seals 40A, 54A, 62A, 70A, 78A, 86A, and94A, respectively. The flanges on the impactor cups are also sealed withtear drop shaped seals. In addition to the seal 34D, the cups 46, 58,66, 74, 82, 90, and 98, are sealed with seals 46D, 58D, 66D, 74D, 82D,90D, and 98D, respectively.

[0064] The cover 24 is hinged to the base with a pin that is springloaded to permit some desired resilient movement perpendicular to theseal plate to provide compression of the seals on the seal plate 30. Thehinging between the cover 24 and the base 25 may be made so that ascompression of the seals on the seal plate 30 occurs, the surfaces thatengage the seal plate, namely the flanges on the impactor cups and theunder surface of the cover, remain parallel.

[0065] As shown schematically in FIGS. 1, 2 and 4, the base 25 has aplurality of upright hinge posts 100, that are spaced along the hingingedge of the base and cover, and the cover has sets of flanges 101, thatfit on the opposite sides of the respective posts 100. The flanges 101carry a pivot pin 101B that passes through a slot 100B in each of theupright posts 100. The pin is urged downwardly with a spring loaded,threaded plunger 102 that is threaded into a bore in the respectivehinge posts. The spring loaded plunger is a purchased unit that has aninternal spring and a centering point at the lower end thereof thatrides in a groove in the pin 101A. This will keep the pin centered andheld in the hinge post 100.

[0066] In order to have an adequate compression load on the seals, a camtype latch assembly 104 is utilized, and is shown in FIGS. 2 and 4,primarily. The latch assembly 104 is supported on ears 104A that are onthe cover member, through first pivot arms 104B. The hinge members orears 104A have pins 104C that permit the arms 104B to pivot upwardly anddownwardly. The solid line position in FIG. 4 shows the cam latchassembly 104 in locked position, and the dotted line position shows itreleased.

[0067] A latch handle assembly 105 is pivoted to the arms, with pins105A. The handle assembly 105 comprises a pair of end arm members 105B,105B as shown in FIG. 2, connected with a handle rail 105C thatcomprises a hand grip, and the handle arms 105B are also joined with alatch bar 105D.

[0068] The base 25 carries a plurality of latch hooks 106, that receivenose portions 105E of the latch bar 105D. The pivots are arranged for anover center latch action. The latch is released by pulling up on handle105C in direction of arrow 108D.

[0069] As shown in FIG. 1, the base 25 has support feet 25F, and at thehinge end, a bracket 108 is provided that can be fixed to the hingebosses 100. The bracket 108 has an upright leg 108A that is rigidlyattached to the lower portion of the leg, and when the unit is turned upon edge, the bracket 108A will support the impactor assembly 10 with thehinge edge downwardly, letting it stand in an upright position with thehandle extended upwardly.

[0070] The bottoms of the cups are supported so they clear thesupporting surface. This means that when the cover is opened, after thetest has been run, tray 36 can be lifted out of the bottom frame,manually or with a fixture. When the tray is lifted all of the impactorcups are removed as a unit. The cups may be placed either in a separatecontainer and sealed, or as disclosed simultaneously processed forrecovering and analyzing the particles in each impactor cup.

[0071] The ability to lift all of the cups at once makes manual ormechanically assisted operation easier, because the cup tray can beinstalled in racks and moved as a unit. The cup tray has locatingflanges 37 that act as feet when the tray is removed. The locatorflanges 37 lap over the edges of the base to keep the tray 36 in place.

[0072] The cups also have outwardly tapered side walls so they can benested and stacked for storage.

[0073] The flow paths are shown essentially in FIG. 3, with arrows 99.The flow path is from the inlet to the outlet. The path is divided intosegments, forming impaction stages, by the nozzles.

[0074] The nozzles and the orifice sizes are selected to provide atleast 5 cut points at all desired flow ranges that are between 0.4 μmand 6.0 μm. In addition, one stage should provide particles between 5 μmand 10 μm. A pressure drop across the impactor of less than 100 inchesof water at the maximum flow rate is desired.

[0075] In FIG. 7, a modified stacked cup design impactor embodying theprinciples of the present invention is illustrated at 130. The impactor130 includes several individual stages. The impactor 130 has an inletnozzle 133 that leads to a first impactor housing 134. The impactorhousings are made essentially identical and vertically stacked so theycan be separated. The direction of aerosol flow is reversed in thevertically adjacent impactor sections.

[0076] The first stage housing 134 has a tear drop shaped chamber 134A.The large end comprises an impaction surface 134E. The flow from theinlet goes through a cross or interstage passageway 134B and through anozzle passage 134C that has a nozzle plate 134D therein. The nozzleplate 134D is for the second stage impactor and has large openings. Theflow will then pass into a second stage impactor housing 136, whichforms a chamber 136A and which has an impactor surface 136E. Asindicated by the arrows, the flow goes through a passageway 136B to anozzle passageway 136C and a third stage nozzle plate 136D, into a thirdstage impactor housing 138. A different size of openings in the nozzleplate 136D can be selected for a different cut point of particles.

[0077] A third stage chamber 138A has an impaction surface 138E, aninterstage passage 138B, a nozzle passage 138C and a fourth stage outletnozzle plate 138D.

[0078] A fourth stage housing 140, again has a tear drop shaped chamber140A and particles from nozzle plate 138D impinge on fourth stageimpactor surface 140E. The flow passes through a passage 140B, a nozzlepassageway 140C and through a fifth stage nozzle plate 140D to a fifthstage housing 142, having a chamber 142A, and an impactor surface 142E.The flow goes through an interstage passage 142B and into a nozzlepassage 142C and through a further small opening, sixth stage nozzleplate 142D to a sixth stage housing 144.

[0079] The sixth stage housing 144 has an impaction surface 144E, in thechamber 144A. The flow then goes through a passage 144B, and through anozzle passage 144C and then through a seventh stage nozzle 144D into achamber 146A of a seventh stage housing 146 with an impactor surface146E. The flow will pass through a passage 146B, a nozzle passage 146Cand a micro orifice filter 146D having openings thereon to achieve thedesired filtering. The flow will impinge on an impactor plate in housing148 which has a chamber 148A that receives the flow from the filter146D. The flow then will pass out through an outlet opening 148C.

[0080] The stacked design of FIG. 7 uses the tear shaped chambers, asshown, for smooth flow, with little dead volume and thus little chanceof having improper cut points. The housings can be separated foranalysis of particles as will be shown.

[0081] A further modified form of an impactor is shown in FIG. 8. Animpactor 170 is cylindrical and the impactor stage housing are removablymounted one above the other, as is common.

[0082] The impactor 170 has an inlet tube 172 that connects to astandard inlet as shown, and flow comes through the nozzle 173 into aninlet or first stage housing 174. Housing 174 has an impactor chamber174A, with an impaction plate 174B aligned with the inlet nozzle 173.The impaction plate 174B is in the center portions of the chamber. Theimpaction plate portion 174B is surrounded by an integral annular nozzlering 174C that has a plurality of orifices or openings 174D arrangedaround the periphery of the chamber 174A adjacent an exterior annularwall 174E. The flow will pass through the orifices or openings 174D intoa second stage housing 176. The plate 174B and nozzle ring 174C frompart of the top wall of the housing 176. The housing 176 has an outerannular wall 176E around plate 174B. Wall 176E has a shoulder 176F thatreceives an end of the housing wall 174E so the two housings removablenest together.

[0083] Housing 176 forms a chamber 176A into which the flow through theopenings 174D passes. Particles above the cut off size impact on thesurface of an annular impaction surface on wall plate wall 176B. Theparticles above the cut point will be collected on this annular surface176B, and the flow in the chamber 176A inwardly toward the center of thechamber 176A and through a center nozzle section 176C in the centerportions of the chamber, which has a pattern of openings or orifices176D therein. The orifices 176D may be arranged in a square or circularpattern.

[0084] The flow through the nozzle openings 176D will enter into third,fourth, fifth, sixth and several impactor stage housings 178, 180, 182,184, 186, and 188 in sequence, with the impactor plate positionsalternating between the center and outer edge annular plate portions.

[0085] It should be noted that the walls forming the impaction surfacesare supported by the outer wall of the underlying housing. Each of thesubsequent housings have chambers 178A, 180A, 182A, 184A, 186A and 188Arespectively, with impaction surface 178B, 180B, 182B, 184B, 186B. Amicro orifice filter 188B is in chamber 188A and leads to outlet 190.The nozzles are shown at 178C, 180C, 182C, 184C and 186C, respectively.The housing walls 178E, 180E, 182E, 184E, and 186E have shoulders 178F,180F, 182F, 184F and 186F, respectively, to support the housing aboveit. The outlet 190 is supported on a cover 192.

[0086] The impactor 170 provides the range of particle cut points asdesired. The annular nozzles and center nozzles alternate betweenstages.

[0087] The impactor assembly 170 can be disassembled by pulling thetelescoping or nesting parts of the housings apart.

[0088]FIG. 9 shows a general cascade impactor that will have a pluralityof impaction plates that would be used in accordance with the processingsequence of the present invention.

[0089] A schematic representation is shown of an impactor, of generalform which is indicated at 192. Stage 1 has a nozzle plate 193, with animpaction plate 193A held in place in a suitable manner. Stage 2, whichis labeled, includes smaller orifices in nozzle plate 194 that providesimpaction of particles onto an impaction surface of a plate 194A, and athird stage includes a nozzle plate 195 that has smaller nozzles whichparticles on an impaction plate 195A. A final filter 196 is illustrated,and an outlet 197 carries the flow out from the impactor assembly. Eachof the impaction plates 193A, 194A and 195A and the final filter 196 canbe individually removed, and are of a suitable size so that they willwork for the processing according to the present invention illustratedin the following figures.

[0090]FIG. 10 is a flow chart that illustrates the process of thepresent invention for recovering samples, and performing other functionsthat are carried out. The invention relates to equipment that providesmechanically assisted operation, by recovering samples from a pluralityof sample trays or impactor plates at a time, preferably using a tray ofcups from the first form of the impactor, and a method of processing thesamples more efficiently in a laboratory or industrial setting. Thefirst step 200 is to classify particles in a typical impactor with aplurality of impactor plates. These can be the cups that are shown inthe first form of the invention or individual plates in a multi-stageimpactor that are illustrated in the previous figures. The cups orimpactor plates will receive an anti-bounce coating, as represented at216. The anti-bounce coating can be done right after washing theimpactor places, in a continuous process.

[0091] The particles are classified into individual impactor sections,whether it is in a tray of several cups as a unit, or individualimpactor housing or impactor plates. The next stage is to remove a trayof a plurality of impactor cups such as that shown at 202 or,alternatively, if separable plates are used placing a plurality ofplates, or individual housing sections into a multi-compartmentcontainer as indicated at 204. After either step the operator has aplurality of impactor plates having classified particles therein thatcan be handled as a unit.

[0092] The next step is to apply solvent to the plurality of impactorplates or compartments simultaneously as indicated at 206. This again isdone with a plurality of samples, generally up to approximately eightsamples.

[0093] Then, the plurality of plates (samples) are agitated as indicatedat 208 with the solvent. This is done with a machine that agitates allof the multiple samples at once until the particles dissolve. Then thesolution containing the components of interest is removed, as indicatedat block 210, and the samples of interest are analyzed. This isindicated at 212. This is normally done in a high performance liquidchromatograph (HPLC).

[0094] Once the sample of the solution from each impactor plate isremoved, the impactor plates or cups are washed, and this also can bedone with a plurality of impactor plates at once. The impactor platescan be cups or housings, as well as flat plates. This is indicated atstep 214 in FIG. 10. Anti-bounce coatings can be applied as indicated atbox 216, and then the plates, cups or housings are ready for the nextsequence of operations by putting them into a multi-stage or cascadeimpactor and classifying particles.

[0095] Various other alternatives and auxiliary operations can takeplace, such as weighing the individual impactor plates on electronicbalances, as indicated at 218. This can take place after the trays havebeen removed, and then also after the samples have been removed at stage210 to insure a known measure of liquid solvent. Volumetric measurementwith a syringe is normally accurate enough.

[0096]FIG. 23 provides a detailed chart of various functions involved inthis process for particle classification, particle dissolution, sampleacquisition, washing and drying.

[0097] As shown in FIG. 11, the tray 36 from the first form of theinvention can be lifted out of the impactor, leaving all of theindividual impactor plates or cups in place. As shown, the cups 34, 46,58, 66, 74, 82, 90, and 98. Thus, there are eight impactor plates formedby the cups that are lifted as one unit, after the impaction run hastaken place, with all of the classified particles or aerosols carried inthe cups. The cups are held in place in the trays by their respectiveflanges indicated at 34A, 46A, 58A, 66A, 74A, 82A, 90A, and 98A.

[0098] The tray 36 and cups are then moved as a unit to a dissolutionstation indicated at 224 in FIG. 12. The sectional view is taken on12-12 in FIG. 11, so only four of the cups are shown. The basic form ofthe dissolution station includes a carrier or frame 226 that hascentered support shafts 228 at opposite ends that are co-axial, and willpermit rocking the carrier, tray 36 and cups about a generallyhorizontal axis. The shafts 228 can be supported on bearing posts 230,at least one of which has a removable top, to permit the carrier 226 tobe inserted and removed from those posts when desired. The carrier 226has a plurality of openings shown at 232, which are shaped, andoriented, to receive the egg or tear drop shaped cups carried by thetray 36, as shown in FIG. 11. The tray 36 then rests on the flat uppersurface of the carrier or frame 226, with the impaction plates in theform of cups positioned in the openings 236. Then, a cover plate 238 isplaced over the flanges 34A-98A of the respective cups, and clamped inplace. Schematically shown is a stud 240 passing through an opening inthe tray, and a wing nut on the stud 242 for clamping. It is to beunderstood that automatic or spring loaded clamps can be utilized. Ifdesired suitable seals can be placed to seal along the cup flanges.

[0099] A reversible motor 244 drives the shaft. The motor is controlledby a controller 246, which can include a timer. The cover plate 238 hasa series of small openings 247 therein, that align with the respectiveimpactor plates formed as the cups 34-98, and a solvent is thenintroduced through these openings 247 with a suitable solvent dispenser,as shown schematically a syringe 248 or a manual pipette. The syringe248 can be manually operated for quickly injecting a desired, measuredamount of solvent into each of the impactor plate cups, or it can beautomatically operated with a robot type, three axis dispensing transferapparatus (see. FIGS. 15 and 16).

[0100] Once the appropriate amount of solvent is in each of theplurality of impactor cups in this form of the disclosure, so theparticles collected are immersed in the solvent, the motor 244 isstarted with the controller 246, and carrier 226 is then rocked back andforth about the axis of the shafts 228, generally as shown in FIG. 13 indotted lines, from the solid line position. The cover plate 238maintains the cups in position, and the solvent is then permitted tointermix adequately with the classified particles that are in the cups,until the desired component of interest has been dissolved.

[0101] Then, the motor 244 is stopped, and a clean syringe such as thatshown at 248 is dipped into each of the individual cups through theopenings 247 and a sample that is to be analyzed is withdrawn by suctionfrom the syringe or a pipette. Typically 1 ml is withdrawn from each ofthe samples and put into an HPLC vial. This dispensing can also be doneautomatically with an automated handler as will be shown. The wastesolution can be manually dumped, or the motor 244 driven to dump thewaste solution automatically under control of controller 246, the wastealso can be suctioned out with a manual pipette, syringe 248 orautomatic syringe.

[0102] When an impactor plate that received classified particles is aflat plate, or as shown in the other forms of the impactors, is made upof individual housing segments that are stacked one on top of the other,and can be removed, a carrier that has closed bottom chambers of size tohold the individual impactor plates or the individual impactor housingsections may be used. As illustrated in FIG. 14, a multi-compartmentcarrier 260 is supported in a frame 262 that has shafts 264 thereon,that mount in bearing supports 266, as in the previous showing in FIG.12. The carrier 260 has a plurality of chambers 268 formed therein,which have closed bottoms, and which are liquid tight. A plurality ofindividual impactor plates that are indicated at 270, one in eachchamber. The flat plates are provided in many cascade impactors andshown in FIG. 9. The individual plates are put into the plurality ofchambers 268.

[0103] If the individual vertically stacked impactor housing sections ofFIGS. 7 or 8 are utilized, the chambers 268 can be made is suitable sizeand shape to receive the entire housing chamber, so that the particlesin each interior chamber, which is open when the housing sections areseparated, will be subjected to the solvent that is introduced.

[0104] In this form of the invention, a cover plate 272 is held over thechambers 268 in a suitable manner, such as with a stud and wing nut asshown in FIG. 12, or with suitable latches. The cover plate 272 has aseries of openings 274 that overlie and are aligned with the individualchambers 268, and into which a measured amount of a liquid solvent canbe introduced using a syringe such as that shown in 276. The syringe canbe manually or automatically operated and positioned so that the end ofthe syringe inserts through the openings 274 and injects the amount ofsolvent required into each of the chambers containing the substrate orimpactor plate with the particles to be analyzed.

[0105] A variable speed motor 280, operated by the controller 246 can beenergized, and the carrier can be rocked as shown in FIG. 13, foragitating the solvent and particles. In this case, the solvent is alsoindicated in the chambers 268. The impactor plates 270 are immersed inthe liquid solvent and the rocking motion will cause the solvent to washover the impactor surfaces and intermix with the particles fordissolving the desired component from the particles on the impactorplates.

[0106] A sample of the solution containing the solvent and the dissolvedcomponent that has been dissolved will be removed from each chamber, andthe samples will be transferred to vials for the appropriate analyzationinstrument. This can also be done automatically using known robot typeequipment.

[0107] In FIGS. 15 and 16, a robot arm type liquid handler and injectoris shown schematically. Such devices are available commercially, forexample, Gilson, Inc., of Middleton, Wisconsin makes handler arms thatwill operate along three axes using a programmable controller forinjecting one or several samples at the same time into one set ofreceptacles, and can be used for injecting solvents into the chambersused in the dissolution station, and then subsequent to the dissolvingof the desired components, moving syringes into the chambers andextracting the solvent, as shown with the schematically illustratedsyringes. The syringes are held in supports that are mounted on armsthat will move to desired locations in X-Y coordinates in accordancewith a computerized program and will lower the syringes along a Z axisinto the chambers and then move to dispense the samples into vials heldin a holder at a known position for analysis. Multiple probe handlermodel 215, made by Gilson, Inc., have the desired characteristics.

[0108] In FIGS. 15 and 16, a liquid dispenser and handler is illustratedgenerally at 284. While the frame is not shown in full, it is to beunderstood that the rail is supported by a frame 285 that couples to atable 285A forming part of the frame, and is operated through thecontroller 246, in a suitable. manner. A fixed rail indicated at 286extends transversely across the handler, and as shown in FIG. 16, thefixed rail has a laterally moveable arm 288 driveably mounted thereonusing a suitable mounting hub and drive, again which is commerciallyavailable, operated by a motor 290, and controlled by controller 246.

[0109] The laterally moveable arm 288 is driven along rail 286 and inturn has a probe support block 292 thereon, which is driveably mountedon the moveable arm 288 for movement in a second axis along arm 288,perpendicular to the axis of the fixed rail 286. The block 292, in turn,mounts a vertically extending syringe probe 293, which has a slidingblock 294 that can be driven up and down along the syringe probe 293,using a suitable motor 295, so that a syringe 296 supported on the block294 can be moved vertically along probe or arm 293 to a positionoverlying one of the openings 274 in the cover plate 272 of the carrier260 illustrated in place on table 285A in the dissolution station. Thecarrier 226 for the cups also could be mounted on the table. The syringeis operated with an actuator 297 under control of the controller 246.

[0110]FIG. 16 is a plan view of the handler, showing the carrier 260 inposition but with the cover 272 removed. It has the chambers 268 forreceiving circular impactor plates. The showing in FIG. 16 is schematicand not necessarily to scale. It can be seen that the carrier 260 (or226) is supported on table 285A underlying the vertically extendingprobe 293. By properly programming the controls 246 the various drivemotors will move the arm 288 along rail 286, the probe 293 along arm288, and the syringe hub vertically along probe 293, when programmedwith the location of the chambers 268 in carrier 260 and with thelocation of associated vials 302 in a rack or tray 300. The syringe 296is moved as programmed. The syringe will be moved to positions overlyingthe openings 274 and initially inject solvent into the chambers 268 ofthe dissolution station carrier supported in place. After the rocking ormixing motion to dissolve the particles of interest, the syringe 296 canbe relocated at a desired opening 274 and chamber 268, lowered anddriven by actuator 297 to draw out a desired amount of the solution,which would include the dissolved particles or components of interest,and then moved to the tray support 300 that supports a number ofindividual HPLC sample vials 302 in desired coordinate positions thatcan be programmed into controller 246, and deposit the correct solutioninto a designated vial.

[0111] By using this type of a handler, the samples that are to beanalyzed in an HPLC 299 can be quickly transferred to the vials and thenthe vials taken to a conventional chromatograph. More than one syringe296 can be mounted on the vertically moveable block 290.

[0112] As an alternative to the use of a rocking carrier that will“slosh” the solvent across the impactor plates for aiding in dissolvingthe desired components from the particles, manual rocking and otheragitation can be used. FIG. 17 shows an alternative form of agitation ofa solution for dissolving the aerosol suitably. While a singledissolution chamber is shown in FIG. 17, it can be understood that thesame type of carrier that would hold the tray 36 and the impactor cups,or a number of compartments for a plurality of sample substrates orimpactor plates at one time would be used. In this form of theinvention, a carrier 310 has chambers 312 formed therein, as shown, andis supported in a suitable manner relative to a framework. A cover 314is used to enclose the chamber 312, and a suitable solvent indicated at316 can be introduced in a suitable manner as described. The impactorplate or substrate 318 carrying the classified particles is shown inchamber 312. A piston and outer cylinder 320 have an outlet connected toa dip tube 322 that is in the individual chamber 312. Moving the pistonup and down with a reciprocation drive, as shown by the block 324, sothat the piston will move in opposite directions indicated by the arrowadjacent the drive block, will cause the fluid to move in and out of thedip tube, 322. The movement of the piston causes liquid to be drawn intoand expelled from the dip tube 322 to agitate the solvent 316 andaccelerate the dissolution of the particles on the plate 318 in thesolvent. An ultrasonic or mechanical vibration transducer shown at 326also can be connected to the carrier 310 to provide ultrasonic vibrationor energy or mechanical vibrator in the liquid solvent 316 to furtherenhance the dissolution process.

[0113] Following the dissolution of particles, the desired volume of theliquid sample can be transferred by an automatic or manual transfersyringe or pipette to a suitable vial, using the apparatus previouslyshown and explained or doing it manually.

[0114] In FIG. 17, a piston is shown a create a vacuum to draw liquidsolvent up into the dip tube, and to provide a pressure to discharge theupwardly drawn liquid back into the chamber or cell 312, this can alsobe done by alternately connecting the dip tubes to a source of vacuumand a source of pressure through solenoid valves. For example, a rotaryvalve that alternately connects between pressure and vacuum can bedriven, and the plurality of chambers or cells can be agitated as thevalve is driven to alternate pressures in a dip tube.

[0115]FIG. 18 is a schematic representation of one way to measure theamount of solvent dispensed and recovered for record purposes. Aquantity of solvent can be dispensed into a chamber of a separatecalibration cell generally indicated at 328. Cell 328 is supported on anelectronic balance 332 so that the amount of solvent indicated at 334can be weighed. The solvent volume dispensed into the dissolutionstation can be checked by dispensing solvent into this cell 330,weighing it with the balance 332, when beginning a sample recoverycycle, placing the solvent into a chamber for dissolving particles, andat the end re-weighing the solution, so that any change in volume in thecycle will be determined. An average value can be used.

[0116] The bases that are shown in FIGS. 12 and 14, for example, aremade so that they will accommodate the cup tray, or impactor plates, andthere is then a gentle rocker or optional mechanical or ultrasonicagitators can be used. The covers, with the holes in it allow thesyringe to provide introduction of liquids, and removal of liquids. Inoperation, the user places the cup tray in the base and closes the lid,or places the impactor plates in the chambers and closes the lid. Theliquid handler can then dispense the solvent into each cup, and this canbe automatically done as shown. Dissolution takes place, either with thegentle rocker that is shown, the ultrasonic agitation, or mechanicalagitation. The liquid handler, then as shown in the three axes arm, thenremoves the samples to HPLC vials. Optionally, the liquid handler can beprogrammed to come back and suck out waste solutions, with the rockerpositioned so that base is slanted and the liquid will go over to oneside of the cups or one side of the chambers. This can be combined withan automatic dish washer or clean up appliance.

[0117] In the semi automatic process the individual substrates orimpactor plates can be coated with an “anti-bounce” or slightlyresilient material, such as a silicone oil, as is well known. This isdone before impaction, and in a continuous process would be done afterthe cups or impactor plates had been cleaned. FIG. 19 illustrates acoating station showing cups that are carried in the tray 36 in ahousing for coating. The eight cups can be essentially coated with onemanifold or housing that would overlie the cups held in the frame. Ofindividual impactor plates or impactor housing as shown in FIG. 7 areused, framed with chambers on which the dispensing manifold is mountedcan be used.

[0118] The anti-bounce coating station apparatus 340 includes a supportor frame 342 for supporting the impactor cups, or the tray 36 filledwith cups. A single cup shown at 344 is supported on its flanges on thecup tray 36 and then on the frame or the support 226, which can bemounted for rocking movement. A manifold body 346 is positioned over thecups, and can be clamped into place to the frame 226 in a desired manneras shown at 347. The coating manifold body 346 has openings 354 aboveeach cup 344 for a pipette or syringe 384 to deposit solution directlyinto each cup 344. The dispenser 348 has an outlet tube that fits intothe opening 354 and a piston 352 that moves up and down in the syringebarrel. A coating solution is introduced through the passageway 354. Thecoating material can be kept in a reservoir in the handle and introducedinto the cups with valves that permit the liquid to flow into the cups.

[0119] The manifold body 346 has a gas or air duct 362 open to each cup.The duct 362 extends across all of the cups on each tray, and isconnected to an air or gas source 364 through a suitable conduit andopening 360. The duct 362 is open to the cups 344, and an exhaust ductis provided on an opposite end of the manifold so the air or gas can bedischarged. Each cup or chamber holding an impaction plate would have anindividual passageway 354, but as shown all the cups are connected inparallel to the large gas or air duct 362.

[0120] The anti-bounce material introduced into the cups is knownmaterial, for example a mixture of silicone oil and hexane. The solutioncan be drawn into the dispenser 348 by raising the piston 352, and thenupon reversal of the piston 352, the material will be discharged intothe vertical passageway 354 and into the respective cup. Since thecoating material is liquid it will flow across and cover the impactionsurface of the cup. The support 226 is rocked as shown in FIG. 12 whilethe solvent in the coating mixture is vaporized and drying occurs. Theair, which can include other gases, such as dry nitrogen, from the airsource 364 will exhaust solvent (hexane) vapors from the coatingmaterial out through an air discharge opening like are inlet opening 360at the other end of the manifold. The vapors can be routed to a hood orsolvent recovery system. The openings 354 are small and, do notdischarge substantial amounts of vapor. Once the solvent is exhausted,there remains a uniform tacky coating of the appropriate thickness onthe bottom surface of the cup or other impactor plate or substrate 344.By rocking the support, the impaction surfaces are all coated to auniform thickness. The manifold can be sealed on the cup flanges withO-rings to avoid spillage.

[0121] As part of the sample recovery and cleaning process, a combinedstation for sample acquisition, primarily, and alternately also forwashing the impactor plates or trays, which are illustrated in FIG. 20.FIG. 21 is an inverted plan view taken on line 21-21 in FIG. 20 of themanifold plate of assembly that is used for particle dissolution, andsample acquisition and waste solvent disposal primarily, and withsuitable correction for washing and rinsing substrates. In this form ofthe invention, a particle dissolution and sample acquisition/wastesolvent disposal station is illustrated generally at 370, and it alsocan be used as a wash and rinsing station with appropriate manifoldducts. The assembly includes a manifold 372 that forms a cover over abase or substrate carrier 374. The base 374 has a series of openingstherein indicated at 376, that are used for receiving the individualcups from the impactors shown in FIGS. 1-6. These cups are indicated bygeneral number 378, in FIG. 20.

[0122] As can be seen, cup 378 has a flange 378A that is supported onthe tray 36, from the first form of the invention, and eight of thesecups then can be processed as a unit, after impaction, so each of thecups 378 includes particles as desired.

[0123] The manifold cover 372 then can be clamped in place with suitableschematically shown clamps 380, at desired intervals along the edges ofthe manifold and frame body 374 to hold the two parts together, and holdthe flanges sealed. Suitable resilient seals typically shown at 371 areutilized. These seals can be pneumatic seals or soft O-rings that sealwith low compression as shown previously.

[0124] If the station 370 is going to be used for dissolution of theparticles for obtaining samples that are desired, a suitable solvent canbe injected manually or automatically into each cup or compartmentutilizing a syringe 382 through the individual openings 384 that leadinto the recesses 386 forming chambers in the manifold over theindividual cups 378. There would be eight of the openings, and each canhave a check valve in them if desired, to prevent solution from sloshingback out the openings 384 as illustrated schematically. The check valveswould permit liquid to be injected, but would prevent it from beingexpelled. A simple elastomeric flap valve can be utilized, that can bepenetrated by the end of the syringe 371.

[0125] The frame or body 374 has shafts 386 at opposite ends thereof, asillustrated at FIG. 21, and a motor 388 can be used for reciprocatingand driving the body 374, including the manifold cover about the axis ofthe shafts for agitation of the solution and dissolving of thecomponents of interest that are in the cups 378.

[0126] Once the dissolving is done, and adequate dissolving of thesolution has occurred, the motor 388 can be used for tilting the samplerecovery station 370 approximately 45° in a clockwise direction shown inFIG. 20, as illustrated by the dotted lines, and a liquid solution thatwould include the solvent and other components of interest will drainfrom the cup 378 (there are eight of these cups) into a corner of therespective recess 386, through sample recovery passageways shown at 390and 392. These passageways 390 and 392 open to vial holding openings390A and 392A, which are of size to receive threads so that a neck of asample recovery vial shown at 394 can be threaded into, or frictionfitted into, the recesses 390A and 392A. The bores or openings 390A and392A have vent tubes 396 held therein. The vent tubes 396 extend intothe interior of the respective vial and permit air to vent out, so thatwhen the body or frame 374 is brought back to its horizontal position,as shown in FIG. 20 in solid lines, the sample that had drained throughthe passageways 390 and 392 would be carried in the vials or bottles394. In this position, and then after samples have been placed in thevials at a suitable amount of material for analysis, the vials can bemanually removed, and taken to the analyzation station for analyzing thesamples recovered.

[0127] The vials can have screw caps that are fiction fitted into theopenings 390A and 392A, and in the other openings for the eight cupsthat are in assembly, so a robot arm could grip the vials and removethem from the opening. Adequate clearance would be provided relative toany supporting surface. The bearings for the shafts 398 would be onpedestals that would raise the frame 374 upwardly above the supportingsurface sufficiently so that the tilting could occur, and that the vialscould be removed easily.

[0128] After the samples have been decanted, the cups can be washed inplace, in a number of different ways. As shown, the manifold cover 372has an interior passageway shown at 400, that extends all the way alongthe length of the manifold cover 372. The passageway 400 would beconnected with short passageways 404 to the recesses 386 so that asupply of water indicated at 402 could be provided to flush theunderlying cups, sufficiently to provide cleaning. The cups could bedrained into vials that were used for waste, or can be removed afterbeing flushed with water and drained manually. However, putting in alimited amount of water into the cups and then rocking the cups back andforth if desired, drain passageways indicated at 408 can be providedover each one of the recesses 386. The passageways have check valvesthat would permit liquid to be exhausted outwardly, as indicated by thearrow into a duct 409, but prevent liquid from moving inwardly, so thatby tilting the frame 374 counterclockwise to a position where it wassubstantially inverted, the chambers that were formed by the recesses386 and the cups 378 can be permitted to drain. The duct 409 isconnected to a suitable disposal hose or conduit and to drain.

[0129] Finally, if desired, drying air or hot nitrogen enriched air canbe introduced through a conduit 412 that has branches leading to theindividual cups, again with check valves that would prevent outflow fromthe cups, but would permit air to be blown into the individual cups.This passageway is a passageway that is connected in parallel to each ofthe recesses 386, and would cross the narrow ends of the recesses sothat air could be blown in and then exhausted out through the wastepassageways for air discharge. The duct 409 could discharge air to thedrain to atmosphere, or to a filter for filtering the air beingdischarged.

[0130] In this way, a combined sample recovery station and wash stationcan be utilized for automating the process using the eight cups, or someother number of chambers in a suitable base such as that shown for thecarrier 260, that would have a cover manifold similar to 372 mountedthereon.

[0131] The cups shown, and the impaction housing and individual plates,are impactor components that have impaction surface on which particlesare collected. FIG. 22 shows a modified, manual dissolution and sampleacquisition station.

[0132] In FIG. 22, the manifold shown in FIG. 20 is simplified, andprovides the supports for the vials, and the recesses above the cups butnot the ducts for water and air. The manifold can be clamped or heldonto a body containing the individual cups, and then gently rocked,after manually adding solvent into the cups, for dissolution of theparticles. Then the assembly is tilted for sample acquisition in each ofthe individual vials.

[0133] The manifold 370A includes the recesses 386, that mate with thebase 374 and can be held in place on the base overlying the cups 378.The edges of the cups will be sealed with suitable seals. In this formof the invention, the cups can be filled manually with a suitablesolvent before placing the manifold on the cups, or the manifold canhave openings shown at 384A that will permit injection of material froma syringe 381 or pipette manually into each of the individual cups. Theother portions of the manifold are as previously described, includingthe decanting passageways 390, 390A and 392 and 392A. The vials 394 canbe put into position, and then the base 374 and the manifold 370A gentlyrocked manually until particles in the individual cups have beendissolved. The seals 371 will seal the cups to avoid spilling.

[0134] When the dissolution step is completed, by gently rocking thebase and manifold 370A or if desired by vibrations and the like, thesamples can be acquired by tilting the base and manifold to drain thesolvent that has been introduced along with the dissolved particlesthrough the passageways 390 and 392 into the respective vials 394, whichthen can be removed manually and sent for analysis.

[0135] This manual work station, thus is intended primarily forassisting an operator in performing the required manual steps. Thewaste/wash/dry functions can also be performed. The base 374accommodates the cup tray and the cups 378, and as shown it can berocked gently manually, or optionally with the mechanical or ultrasonicagitators that have been described. The manifold 370A has the decantingpassageways and vial holding outlets, and the seals that will seal inthe cup flanges to ensure the solvent will not leak.

[0136] In FIGS. 23 and 24, the support 226 supporting tray 36 and thecups forming impactor plates has a wash and dry manifold 400 supportedover the top. The manifold can be Plexiglas and has a longitudinallyextending passageway 402 connected to a water or solvent source 404. Thepassageway 402 is zigzagged so each opening 406 that opens to arespective cup overlies a portion of the cup. The passageway 402discharges out the opposite end of the manifold from the connection tothe source. A valve 408 can be used to restrict outflow so the amount ofwater discharged from opening 406 can be regulated.

[0137] A longitudinally zigzagged drying gas passageway 412 is alsoformed in the manifold 400 and it has a separate opening 414 over eachcup. The passageway 412 is connected at one end to a dry gas source 416.When washing or rinsing the cups manually, water is introduced throughpassageway 402 and the manifold can be held in place and the cupsagitated or rocked to wash the cups. The manifold can then be lifted andthe cups drained. The manifold can be then placed over the cups againand a dry gas such as hot nitrogen enriched air or air is introducedthrough the passageway 412 for drying the cups. The cups are then readyto use again. No seals on the cups are needed for manualwashing/rinsing, but can be used if desired.

[0138] As a summary of manual operation, the user places the cup tray 36and the cups that are shown at 378 in the base and manually dispensesthe solvent, such as with repeating pipettes or the syringe 381, andthen the manifold 370A can be clamped in place or otherwise closed overthe cups. Dissolution will take place either with the gently manuallyrocking, or with the motor driven rocker, the ultrasonic agitation, orsome mechanical agitation. The user then can decant the samples into thevials manually, by tilting the base, and once the vials are removed, theuser can attach liquid waste line fittings in place of each vial fordraining the remaining solvent and then washing and flushing the cupsand the rest of the passageways in the manifold. After waste iswithdrawn, and rinse, wash, rinse, dry cycles can take place, asdesired. Air can be introduced into the vial passageways by individualfittings or a manually placed air hose.

[0139] The connections can be made to a waste drain for tilting themanifold by tilting them into the bores where the vials are provided,and afterwards the washer rinse water can be introduced through thebores in a suitable manner.

[0140] In the form of FIGS. 23 and 24, the tray is covered with amanifold for introducing a solvent or water with detergent, rocking thetrays, emptying them and then drying.

[0141]FIG. 25 is a summary chart showing various combinations of methodsthat can be utilized for carrying out the principles of the presentinvention. The methods of coating, which would be application of theanti-bounce coating, can be used in connection with any one of themethods of solvent addition, the methods of particle dissolution, themethods of sample acquisition, the methods of waste disposal, themethods of washing, or the methods of drying. Thus, there are largenumbers of combinations that can be made.

[0142] By way of example, the anti-bounce coating can be done withmanual pipetting, the solvent can be added with automatic pipetting, thedissolution can be done with gentle agitation, the sample acquisitioncan be done with an automatic syringe, the method of waste disposal canbe done with automatic dumping, the method of washing can be manual, andthe method of drying can be hot nitrogen enriched air. It can be seenthat any one of the different selections can be used with any one of theother selections in each of the columns. It should be noted that themethods of dissolution include direct contact rubbing, which was notpreviously explained, that means that the solvent can be rubbed againstthe particles, and recirculation would include pumping the material ormoving the material a number of times against the particles fordissolution.

[0143] In the method of sample acquisition, the decanting step is thatillustrated with the apparatus of FIGS. 20, 21 and 22. Waste disposal bysuction is merely drawing the waste solutions with a vacuum, or with asyringe that sucks the material out. The other steps are self-evident,it is believed.

[0144] Manual operations of the described work station in FIGS. 12-14uses the components for assisting an operator in the required manualsteps. FIGS. 22, 23 and 24 are also designed as a manual station. Thedissolution, sample acquisition, and waste/wash/dry functions arecombined in the devices of each of FIGS. 12 and 14 into one unit. Thebase that accommodates cup tray or the impactor plates can be manuallyrocked, or the motor for the gentle rocker or optional mechanical orultrasonic agitators used. The cover has decanting passageways and vialports, as shown in FIG. 22 and also accomplishes an O-ring seal. Theuser places the cup tray in the base (FIG. 12) or places the impactorplates in compartments (FIG. 14), and manually dispenses solvent (likelywith a repeating pipette). The cover or lid can be put on if not doneearlier. Dissolution takes place, either with manual rocking, themotorized gentle rocker, ultrasonic agitation, or mechanical agitation.User then decants or removes and places the samples into vials.

[0145] In connection with FIG. 22, once vials are removed, the userattaches liquid waste line fittings in place of each vial and can tiltthe unit to dump waste, then the rinse, wash, rinse, dry cycle can becarried out as desired.

[0146] For dissolution of the particles, the supports for the cup orimpactor plates or tray can be rocked slowly back and forth, about 5 to20 degrees, particularly in relation to FIGS. 12 and 14. The covers willprevent contamination and eliminate any meaningful solvent loss; thecover does not need to accomplish a liquid seal, and the cover may haveholes in it to allow addition and removal of solvent. The particles canbe manually rubbed by direct contact using a pad on a handle.

[0147] The Ultrasonic Dissolver may be made to accommodate cup tray andcups or a base with connections. The base can have electronic connectionso when the cover closes electrical contact is made. In this case thecover also accomplishes a pneumatic seal to avoid splashing andcontamination of neighboring cups.

[0148] The Mechanical Dissolver accommodates the cup tray and the basehas mechanical agitators, such as vibrators. Here too, the lid can beused to start the agitation and to accomplish a seal to avoid splashingand contamination of neighboring cups.

[0149] Washing can also be done by placing the cups in a kitchendishwasher using dish detergent.

[0150] Although the present invention has been described with referenceto preferred embodiments, workers skilled in the art will recognize thatchanges may be made in form and detail without departing from the spiritand scope of the invention.

1-5. (Canceled)
 6. A method of cleaning a plurality of impactorcomponents having impaction surfaces which are enclosed, includingproviding a manifold for injecting liquid into an enclosure, includingthe impaction surfaces, draining the liquid after washing, and providinga drying fluid to the enclosure for a plurality of such impactionsurfaces simultaneously while held in a common carrier.
 7. The method ofclaim 6, wherein the impaction surfaces are part of a cup shapedcomponent, and sealing the cup shaped device relative to a manifoldcarrying ducts for introducing liquid, providing a drain, andintroducing drying fluid.
 8. The method of claim 6, including providinga manifold having passageways for liquid and gas leading to each of theimpaction surfaces. 9-14. (Canceled)
 15. The apparatus of claim 23wherein the cup impactor devices hold particles on impaction surfaces ofthe cup impactor devices, after the particles have been classified as tosize in an impactor, further comprising a support having a plurality ofreceptacles for receiving the tray and cup impactor devices carrying theparticles, said support being mounted for movement, and an overlyingcover on the support over the tray and cup impactor devices, the coverincluding openings for introducing a solvent to immerse each of theimpaction surfaces.
 16. The apparatus of claim 15, wherein said cupimpactor devices comprise individual impactor cups, and wherein saidsupport holds individual impactor cups having the impaction surfaces onthe interior thereof, and a clamp to clamp the cover against the cups inposition in receptacles of the support.
 17. The apparatus of claim 16,wherein each of the cups has a flange around the periphery thereof, thetray openings permitting a majority of the cup to pass through theopenings and so the tray supports the cup on the flange, the supportsupporting the tray with the cups protruding into the receptacles of thesupport, the cover engaging the flanges of the cups and holding thecups, the tray, and the support as a unit.
 18. The apparatus of claim 17and seals around the cups engaging the flange and sealing the cupsrelative to the cover.
 19. The apparatus of claim 18, wherein the coverhas a plenum chamber open to each of the cups.
 20. A sample recoverystation for recovering samples from a plurality of impactor surfaceshaving classified particles on the surfaces, comprising a support framehaving a plurality of openings, a tray for supporting a plurality ofcups with portions of the cups protruding from the plane of the tray,the support having a surface holding the tray with the cups in positionin receptacles in the support, a manifold cover held relative to thesupport and including recesses overlying each of the cups, a vialholding bore formed in the manifold tray, and having an axis that isinclined relative to the plane of the tray in a first direction, aconnecting bore adjacent an edge of the recess in the manifold coveropening to the bore for the vial, and having a axis generallyperpendicular to the axis of the bore, whereby rotating the supportabout a central axis causes the connecting passageway to drain the cupsinto the vial holding bores.
 21. The sample recovery device of claim 20,wherein said manifold cover contains passageways for introduction ofliquid into the recesses.
 22. The sample recovery device of claim 20,wherein said manifold cover includes passageways for permittingdischarge of gases and liquids from the recesses in the manifold cover,and passageways for permitting the introduction of a gas into therecesses of the manifold cover.
 23. An apparatus for handling cup shapedimpactor devices comprising a tray having openings for said cup impactordevices, said cup impactor devices having a body that fits through theopenings and flanges that engage surface portions of the tray around theopenings and prevent the entire cup from passing through the openings,the body of the cup extending through the tray.
 24. The apparatus ofclaim 23, wherein said tray comprises a generally flat plate with theopenings therethrough, and the flanges of the cups being supported onthe flat plate.
 25. The apparatus of claim 23 and a cover member forforming a manifold over said tray and cups, said cover member having apassageway that extends transversely across all of the cups, andopenings from the passageway to each of the cups, the passageway beingadapted to be fitted to a liquid cleaning material source.
 26. Theapparatus of claim 25, wherein said cover has a second passageway opento each of the cups on the tray, and the second passageway beingconnected to a source of a gaseous fluid.
 27. The apparatus of claim 23and a cover manifold for said tray comprising a plenum chamberindividually open to each of the cups, and an opening above each of thecups for introducing a coating material, said tray being adapted to berocked about a longitudinal axis with the coating material in place, andthe plenum chamber being connected to a source of gaseous fluid foreliminating vapors from the coating material. 28-32. (Canceled)
 33. Themethod of claim 6 including the steps of adding a quantity of ananti-bounce coating material into each cup to cover the impactionsurfaces, and providing a flow of drying fluid over the impactionsurfaces to remove vapors from solvents in the coating.
 34. The methodof claim 33, including rocking the cup so the coating material flowsacross the impaction surface while drying.